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Laboratory of Nanoscale Biology

  • About LNB
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    • Electron diffraction of biological specimens
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Dr. Roger Benoit

Roger Benoit

Scientist

Paul Scherrer Institut
Forschungsstrasse 111
5232 Villigen PSI
Schweiz
Telefon
+41 56 310 47 03
E-Mail
roger.benoit@psi.ch

 

Curriculum Vitae

Team

Research Interests

My research focuses on structure-based protein engineering. We explore the structural and biophysical basis of protein interactions, including receptor-drug, protein-protein, protein-toxin, protein-pathogen, protein-nucleic acid and protein-small molecule interactions. We apply structural elements found in natural proteins (molecular biomimetics) to engineer novel fusion proteins (protein nanotechnology) for a wide range of purposes. For example, my team and I have designed and produced fusion proteins containing intrinsically stable helical spacers to (1) introduce large cavities into crystal lattices (for the study of protein dynamics by crystallography); (2) develop self-assembling oligomeric protein scaffolds that display on their surface multiple copies of an epitope of choice at specific angles and distances (for the design of novel vaccines, structural vaccinology); and (3) produce rigid G-protein-coupled receptor (GPCR) fusion proteins that aid structure elucidation by cryo-EM of receptor-drug complexes. We furthermore explore novel fusion proteins as tools for in situ structural biology, both at near-atomic resolution and at the mesoscale (fluorescent sensors for the detection of important mesoscale cellular rearrangements involved in cancer metastasis;  probes for the detection of toxin- or pathogen- receptors on cells; novel fusion proteins for the detection of proteins in large complexes in cryo-EM tomography).

Structure-based fusion protein engineering
Structure-based fusion protein engineering

Preprints


Farnung J., Muhar M., Liang J.R., Tolmachova K.A., Benoit R.M., Corn J.E., Bode J.W.
ATG3 contains a non-canonical LIR motif crucial for its enzymatic activity in autophagy
bioRxiv. 2022; doi: https://doi.org/10.1101/2022.08.02.502437


Collu G., Mohammed I., Lafita A., Bierig T., Poghosyan E., Bliven S., Benoit R.M.
Cryo-EM structure of a single-chain β1-adrenoceptor – AmpC β-lactamase fusion protein
bioRxiv. 2021; doi: https://doi.org/10.1101/2021.09.25.461805


Publications

  • Collu G, Bierig T, Krebs A-S, Engilberge S, Varma N, Guixà-González R, et al.
    Chimeric single α-helical domains as rigid fusion protein connections for protein nanotechnology and structural biology
    Structure. 2022; 30(1): 95-106. https://doi.org/10.1016/j.str.2021.09.002
    DORA PSI
  • Bierig T, Collu G, Blanc A, Poghosyan E, Benoit RM
    Design, expression, purification, and characterization of a YFP-tagged 2019-n CoV spike receptor-binding domain construct
    Frontiers in Bioengineering and Biotechnology. 2020; 8: 618615 (10 pp.). https://doi.org/10.3389/fbioe.2020.618615
    DORA PSI
  • Skopintsev P, Ehrenberg D, Weinert T, James D, Kar RK, Johnson PJM, et al.
    Femtosecond-to-millisecond structural changes in a light-driven sodium pump
    Nature. 2020; 583: 314-318. https://doi.org/10.1038/s41586-020-2307-8
    DORA PSI
  • Krebs A-S, Bierig T, Collu G, Benoit RM
    Seamless insert-plasmid assembly at sub-terminal homologous sequences
    Plasmid. 2019; 106: 102445 (9 pp.). https://doi.org/10.1016/j.plasmid.2019.102445
    DORA PSI
  • Benoit RM
    Botulinum neurotoxin diversity from a gene-centered view
    Toxins. 2018; 10(8): 310 (14 pp.). https://doi.org/10.3390/toxins10080310
    DORA PSI
  • Benoit RM, Schärer MA, Wieser MM, Li X, Frey D, Kammerer RA
    Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C
    Scientific Reports. 2017; 7: 43588 (7 pp.). https://doi.org/10.1038/srep43588
    DORA PSI
  • Heydenreich FM, Miljuš T, Jaussi R, Benoit R, Milić D, Veprintsev DB
    High-throughput mutagenesis using a two-fragment PCR approach
    Scientific Reports. 2017; 7: 6787 (11 pp.). https://doi.org/10.1038/s41598-017-07010-4
    DORA PSI
  • Benoit RM, Ostermeier C, Geiser M, Li JSZ, Widmer H, Auer M
    Seamless insert-plasmid assembly at high efficiency and low cost
    PLoS One. 2016; 11(4): e0153158 (13 pp.). https://doi.org/10.1371/journal.pone.0153158
    DORA PSI
  • Bianchi S, van Riel WE, Kraatz SHW, Olieric N, Frey D, Katrukha EA, et al.
    Structural basis for misregulation of kinesin KIF21A autoinhibition by CFEOM1 disease mutations
    Scientific Reports. 2016; 6: 30668 (16 pp.). https://doi.org/10.1038/srep30668
    DORA PSI
  • Christen P, Jaussi R, Benoit R
    Biochemie und Molekularbiologie. Eine Einführung in 40 Lerneinheiten
    Berlin, Heidelberg: Springer; 2016. https://doi.org/10.1007/978-3-662-46430-4
    DORA PSI
  • Christen P, Jaussi R, Benoit R
    Biomoleküle und ihre Wechselwirkungen
    In: Christen P, Jaussi R, Benoit R, eds. Biochemie und Molekularbiologie. Eine Einführung in 40 Lerneinheiten. Berlin; Heidelberg: Springer; 2016:3-16. https://doi.org/10.1007/978-3-662-46430-4_1
    DORA PSI
  • Benoit RM, Frey D, Wieser MM, Thieltges KM, Jaussi R, Capitani G, et al.
    Structure of the BoNT/A1 - Receptor complex
    Toxicon. 2015; 107(Part A): 25-31. https://doi.org/10.1016/j.toxicon.2015.08.002
    DORA PSI
  • Benoit RM, Frey D, Hilbert M, Kevenaar JT, Wieser MM, Stirnimann CU, et al.
    Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A
    Nature. 2014; 505(7481): 108-111. https://doi.org/10.1038/nature12732
    DORA PSI
  • Kammerer RA, Benoit RM
    Botulinum neurotoxins: new questions arising from structural biology
    Trends in Biochemical Sciences. 2014; 39(11): 517-526. https://doi.org/10.1016/j.tibs.2014.08.009
    DORA PSI
  • Benoit RM, Meisner N-C, Kallen J, Graff P, Hemmig R, Cèbe R, et al.
    The X-ray crystal structure of the first RNA recognition motif and site-directed mutagenesis suggest a possible hur redox sensing mechanism
    Journal of Molecular Biology. 2010; 397(5): 1231-1244. https://doi.org/10.1016/j.jmb.2010.02.043
    DORA PSI

 

Benoit R.M. and Auer M.
A direct way of redox sensing
RNA Biol. 2011; 8: 18-23
DOI: 10.4161/rna.8.1.13555


Meisner N.C., Hintersteiner M., Seifert J.M., Bauer R., Benoit R.M., Widmer A., Schindler T., Uhl V., Lang M., Gstach H., Auer M.
Terminal adenosyl transferase activity of posttranscriptional regulator HuR revealed by confocal on-bead screening.
J Mol Biol. 2009; 386: 435-450
DOI: 10.1016/j.jmb.2008.12.020


Benoit, R.M., Wilhelm, R.N., Scherer-Becker, D., Ostermeier, C.
An improved method for fast, robust, and seamless integration of DNA fragments into multiple plasmids.
Protein Expr Purif. 2006; 45: 66-71
DOI: 10.1016/j.pep.2005.09.022

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Laboratory of Nanoscale Biology

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Anita Strittmatter
Secretary

Paul Scherrer Institut
Department of Biology and Chemistry
OFLC/108
Forschungsstrasse 111
CH-5232 Villigen PSI
Switzerland

Phone: +41 56 310 20 35
Fax: +41 56 310 21 99
anita.strittmatter@psi.ch

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